Fragile X mental retardation is caused by loss-of-function of the FMR1 gene and is the most prevalent inherited form of mental retardation resulting from a single gene defect. The frequency with which this disorder appears (about every 5000 births) and its global distribution make fragile X mental retardation one of the most prominent human genetic disorders. Although it is known that the FMR1 protein is an RNA-binding protein that interacts with a small subset of messages, the identity of these messages and the effect FMR1 protein binding has on such messages is poorly understood. [unreadable] [unreadable] The long-term objective of this proposal is to gain insight into specific biochemical functions of the FMR1 protein through a molecular genetics approach that utilizes the fruit fly Drosophila melanogaster as a model system. The fruit fly has a single orthologue to the human FMR1 gene referred to as dfmrl. The amenability of Drosophila to transgenic studies allows for in vitro engineered mutant alleles of dfmrl to be introduced into flies lacking an endogenous wild-type allele. This experimental approach will allow studies of these mutant alleles for defects in RNA processing, behavior, and neuroanatomy to be performed in a physiologically and developmentally relevant context. These studies will allow an assessment of biochemical processes and modes of regulation associated with dfmrl that will likely be applicable to understanding the in vivo function and regulation of all members of the FMR1 gene family. [unreadable] [unreadable]